Standardization of inhalation provocation tests. Dose vs concentration of histamine

The importance of histamine dose vs histamine concentration in determining the response to inhaled histamine was evaluated by comparing the effect of 30 sec and two min inhalation times on duplicate histamine inhalation tests in 15 asthmatic patients. The histamine provocation concentration required to produce a 20 percent FEV1 fall after 30 sec inhalations (30 sec PC20) was on average 3.6-fold greater than the two min PC20. Individually, ten of the 15 fell within the range of dose reproducibility (+/- one doubling dose), while five subjects fell outside this range, three with 30 sec PC20 less than twice two min PC20 and two with 30 sec PC20 greater than 8 X two min PC20. Seven subjects had duplicate measurements of both 30 sec PC20 and two min PC20; the two min PC20 was more reproducible than the 30 sec PC20 in all seven. The better reproducibility of the two min PC20 is likely due to a more reproducible inspiratory time over the two-minute breathing period. These findings have relevance in standardization of inhalation challenge tests, and in comparing results of such tests done by different techniques.